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Title: Spectroscopic imaging of the compaction and dissolution of model pharmaceutical formulations
Author: Wray, Patrick S.
ISNI:       0000 0004 2706 7192
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Orally administered compressed tablets are the most commonly used dosage form. Understanding the physical and chemical processes involved in drug release from tablets is critical for designing more effective formulations. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopic imaging is a powerful chemically specific and spatially resolved analytical approach. Effective uses for this technology have been found in the field of pharmaceutics, studying the compaction and dissolution of oral dosage formulations. However, the full potential of this technology is yet to be explored. This thesis describes work that further explores the applications of FTIR imaging through the use of model pharmaceutical formulations. The work is broadly split into three sections: quantification of imaging data, dissolution of pH modified formulations and application to structured tablets. The in situ compaction of model drug tablets with different polymer matrices was studied using ATR-FTIR imaging. The choice of polymer strongly affected the distribution of the drug at the tablet surface. X-ray tomography was used as a complementary technique, verifying the distribution of drug particles within the compacted matrices. Statistical analysis was applied to investigate obtaining quantitative data such as particle size and component loading from the image data. Previous work using ATR-FTIR imaging has shown the ability of the approach to detect crystallisation of ibuprofen during dissolution. The dissolution of ibuprofen from HPMC matrices containing pH modifying compounds was studied. FTIR imaging showed that tablets containing acidic compounds slowed the dissolution of crystalline ibuprofen domains. The formation of soluble and insoluble salts of the drug was seen in tablets containing basic compounds. As FTIR imaging supplies both chemical and spatial information it was applied to study structured tablets, both tablet-in-tablet structures and multilayer formulations, in conjunction with visible optical video analysis. The tablet-in-tablet structures were used to create delayed release formulations, in which both the core and shell materials were used to control release. pH resistant formulations were also developed for the release of pH labile drugs. FTIR imaging supplied vital information on the rate of ingress of water fronts, the movement of swelling polymers and the chemical state of the drug. Multilayer formulations were investigated for studies of biphasic release and also in order to compare the dissolution performance of tablets in the custom ATR flow cell with that found in the industry standard USP tests.
Supervisor: Kazarian, Sergei Sponsor: Bristol Myers Squibb ; EPSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral